The goals of this project are to develop and use techniques to transfer genes into primary neuronal cells and to employ antisense technology to control and assess the expression of genes that may be important in neuronal development. Electroporation was used to transfect the reporter genes RSV-beta-galactosidase and RSV-chloramphenicol acetyltransferase (CAT) into cerebellar granule cell cultures. RSV- beta-galactosidase was expressed in both neurons and astrocytes. Assays of these cultures yielded easily detectable CAT activity. Transfection of a beta-galactosidase reporter gene driven by the neuron-specific enolase promoter gave expression predominantly in neurons. Reporter gene pSV-luciferase, which should markedly increase levels of detectable activity, and phosphorothioate-modified sense and antisense oligonucleotides (oligos) are being tested. The oligos, 25 bp long and spanning the ATG site of the gene for the tau protein, are used to inhibit tau expression in order to assess the role of tau in neuronal migration and development.